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A team of researchers at Johns Hopkins University School of Medicine may have discovered a game-changing chemical alteration to a gene that could enable doctors to predict a person’s probability for attempting suicide. If confirmed in future studies with larger samples, a simple blood test could identify this chemical change and offer a crucial new method for suicide prevention. Suicide is one of the top ten leading causes of death, and rates of suicide deaths have not decreased appreciably in 50 years, according to theNational Institute of Mental Health.

"Suicide is a major preventable public health problem, but we have been stymied in our prevention efforts because we have no consistent way to predict those who are at increased risk of killing themselves," said lead author Zachary Kaminsky, Ph.D., who used his 2010 NARSAD Young Investigator Grant to support a part of this work. "With a test like ours, we may be able to stem suicide rates by identifying those people and intervening early enough to head off a catastrophe." Dr. Kaminsky is an Assistant Professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine. The results of this research were published online in The American Journal of Psychiatry on July 30th.

The study began with the researchers focusing in on a mutation in a gene known as SKA2—a gene involved in the function of the brain's response to stress hormones—in brain samples from control subjects and from people with mental illness. From this analysis, researchers including former NARSAD Young Investigator Grantees Jennifer Payne, M.D., and Holly Wilcox, Ph.D., noticed that in samples from brains of people who had died by suicide, levels of SKA2 were significantly reduced. They discovered, within the common mutation of this gene, that in some subjects an epigenetic modification altered the way the SKA2 gene functioned. (Epigenetic changes affect how genes are expressed without altering the underlying DNA sequence.) A more significant level of this modification was found in the subjects who had died by suicide.

Based on its position in stress-relevant gene pathways, the SKA2 gene may be linked to brain functions including inhibiting negative thoughts and controlling impulsive behavior. The researchers reason that if there isn't enough SKA2, or it is altered in some way, the stress hormone receptor is unable to suppress the release of cortisol throughout the brain. Previous research has shown that such cortisol release is abnormal in people who attempt or die by suicide.

In another part of the study, three sets of blood samples from living participants were tested. From the largest sample (325 participants), the researchers found similar epigenetic changes to the SKA2 gene in participants with suicidal thoughts or attempts. From this data, they were able to create a model that predicted which of the participants were experiencing suicidal thoughts or had attempted suicide with 80 percent certainty in the other cohorts tested. Those with more severe risk of suicide were predicted with 90 percent accuracy. In the youngest data set, they were able to identify suicide attempt with 96 percent accuracy—all based on the results of a blood test. The researchers concede that these results are based on relatively small sample sizes and that further validation efforts will be required to support the efficacy of a future blood test.

"We have found a gene that we think could be really important for consistently identifying a range of behaviors from suicidal thoughts to attempts to completions," Dr. Kaminsky says. "We need to study this in a larger sample but we believe that we might be able to monitor the blood to identify those at risk of suicide."

Brain & Behavior Research Foundation President and CEO, Jeffrey Borenstein, M.D., commented in Health Day that "more people die from suicide than from homicide. A test that can better identify people at risk of committing suicide has tremendous potential.” He believes that, "if this finding is confirmed, it would help to ensure that people who are at risk get the treatment they need."

Article comments

Great work. Are you aware of a scientist, Bill Walsh, PhD, of Walsh Research Institute who has identified five depression biotypes through blood testing as well? He presented his studies at the American Psychiatric Association Annual Meeting earlier this year.

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